New Quadrivalent HPV Vaccine Developments

Abstract

Human papillomavirus infection is the most prevalent sexually transmitted disease in the world and is responsible for cervical, vulvar, and vaginal cancers, as well as genital warts. A vaccine against HPV types 6, 11, 16, and 18 has been available since 2006 and has been approved for the prevention of cervical cancer, cervical precancers, and genital warts. Recently, the vaccine also received approval for the prevention of vulvar and vaginal cancers in women aged 9 to 26 years. Although Guillain-Barré syndrome and death have been reported in women who received the vaccine, an analysis of available data by the US Food and Drug Administration found no association between the vaccine and these adverse events. Since post-vaccination syncope is common among young women, providers should ensure that patients remain seated when vaccinated and under observation for at least 15 minutes following vaccination.     

HPV vaccine: Cervarix

Importance of the field: Cervical cancer is a major cause of morbidity and mortality worldwide and is common in relatively young women. Cervical screening programs, while successful if properly carried out, are difficult and expensive to implement, and offer secondary, not primary prevention. Vaccination against the human papillomavirus (HPV), which is the major cause of cervical cancer, is a significant step forward.

Areas covered in this review: The data on Cervarix, the GSK HPV vaccine, are reviewed and placed in the context of HPV vaccination as a whole. A literature review using PubMed listed publications and official product websites has been carried out.

What the reader will gain: The reader will gain an understanding of the issues involved in HPV vaccination and of the data to date.

Take home message: Cervarix has been shown to have high efficacy against disease associated with both HPV-16 and HPV-18. Its antibody response profile allows for optimism regarding the duration of immunity. The fact that it is a virus-like particle, rather than a live-virus vaccine, is reassuring regarding safety, as are the reasonably extensive safety data for the vaccine preparation so far accrued. Cross protection against oncogenic non-vaccine HPV types, in particular HPV-45, may be important in the prevention of cervical adenocarcinoma, which is currently not well served by screening.     

Evidence-Based Practice Model to Increase Human Papillomavirus Vaccine Uptake: A Stepwise Approach

ObjectiveTo increase uptake of human papillomavirus (HPV) vaccination by implementing a stepwise evidence-based practice model to offer HPV education along with a strong provider recommendation to parents of youth and adolescents.DesignEvidence-based practice change model.SettingA nurse practitioner–run, primary care walk-in clinic in a rural area of the southeastern United States.ParticipantsParents of youth and adolescents ages 11 to 17 years.Interventions/MeasurementsEducation targeting parental hesitancy and strong recommendations for immunization was administered by health care providers to parents of youth and adolescents eligible for vaccination. The Parent Attitudes About Childhood Vaccine instrument was used to identify the presence and degree of parental hesitancy. Vaccination uptake was measured and compared to the same time period from the previous year.ResultsData collected from the clinic vaccination log during the same 6-week time period in 2018 identified that four youth/adolescents were vaccinated with the HPV vaccine in 2018. During the same 6-week period in 2019 when the practice change was implemented, 38 parents were approached; 24 met eligibility criteria, and all 24 of their youth/adolescents received HPV vaccination.ConclusionImplementation of an evidence-based practice model that includes standing vaccine orders and reminders and recalls may provide an effective way to ensure completion of the HPV vaccine series. Every missed clinical opportunity to vaccinate youth and adolescents against HPV can contribute to lower vaccination rates and increased risk for genital warts and cancers associated with HPV infection.     

Improving Human Papillomavirus Vaccine Uptake in the Family Practice Setting

Low uptake of the human papillomavirus (HPV) vaccine is a challenging problem in the primary care setting. Interventions are needed to dispel barriers, improve patient education, and increase provider recommendation. The purpose of this quality improvement project was to evaluate the use of a provider-based intervention to help meet this challenge. A survey was used to assess for changes in HPV knowledge, perceived barriers, and vaccine recommendations. The results showed 12% improvement in HPV knowledge and a decrease in perceived provider/system barriers; there was no significant change in recommendations shown. An upward trend in vaccine initiation and completion was appreciated.     

Intervention to Increase Human Papillomavirus Vaccine Initiation Rates in Adolescent Males

The objective of this quality improvement project was to increase human papillomavirus (HPV) vaccine initiation rates among males aged 11 to 21 years old. A multipronged strategy was implemented at a pediatric practice, including an electronic medical record prompt, educational presentation, and monthly e-mail updates to providers. Deidentified HPV vaccine initiation rate data were collected, and a paired 2-sample t test evaluated differences in prepost vaccine initiation rates. HPV vaccine initiation rates increased by 6.5% during the project period. The medical record prompt was identified as most effective by 75% of participating providers. Small gains can be made to improve HPV vaccine initiation rates among adolescent males.     

Increasing Human Papillomavirus Vaccination Rates Among Adolescents: Overcoming Vaccine Hesitancy and Using Practice Improvements

The human papillomavirus (HPV) is responsible for thousands of cases of cancer annually, including cancers of the cervix, oropharynx, and anogenital areas. Since 2006, a vaccine for HPV has been available that offers the hope of dramatically reducing rates of HPV-related cancers. Rates of vaccination for HPV are much lower than rates of other recommended childhood vaccinations, because of difficulties reaching teenage patients and hesitancy toward the vaccine. This article provides recommendations to help pediatric and family practice providers increase rates of uptake of the HPV vaccine among adolescent patients, including communication strategies, and practice improvements that encourage vaccination.     

HPV DNA和HPV E6/E7 mRNA检测在宫颈癌筛查中的应用价值探讨

目的探讨HPV DNA和HPV E6/E7 mRNA检测在宫颈癌筛查中的应用价值。方法选取宫颈病变筛查的受试者407例为研究对象,均行宫颈薄层液基细胞学(TCT)检查,并检测细胞学标本中HPV DNA和HPV E6/E7 mRNA的表达。215例行阴道镜宫颈活检,结合组织病理诊断结果进行统计分析。结果 407例细胞病理学诊断结果:正常范围(WNL)192例(47.17%)、意义不明的不典型鳞状上皮细胞(ASCUS)106例(26.04%)、低度鳞状上皮内病变(LSIL)70例(17.20%)和高度鳞状上皮内病变(HSIL)39例(9.58%)。诊断为LSIL和HSIL患者中,HPV DNA和HPV E6/E7 mRNA检出率差异无统计学意义(P0.05);诊断为ASCUS患者中,HPV DNA检出率显著高于HPV E6/E7 mRNA(P0.01)。215例组织病理学诊断结果:正常109例,阴性106例,包括CINⅠ级44例、CINⅡ级27例、CINⅢ级32例、宫颈鳞癌3例。对于诊断为CINⅡ级、CINⅢ级/宫颈癌患者,HPV DNA和HPV E6/E7 mRNA检测的灵敏度、特异度和阳性预测值差异无统计学意义(P0.05),但HPV E6/E7 mRNA检测的阴性预测值和准确度显著高于HPV DNA检测(P0.05或P0.01)。结论 HPV E6/E7 mRNA检查较HPV DNA检查能更好地评估HPV感染患者宫颈病变恶化风险,联合TCT检测对提高宫颈癌早期筛查和诊断的准确度具有积极意义。     

HPV infections in retinoblastoma: a systematic review

BackgroundRetinoblastoma is the most common primary intraocular malignancy in children less than 4 years. Retinoblastoma (RB) contains about 3%–5% of all childhood cancers. Recent studies demonstrated that interacting between RB tumor suppressor and oncoproteins of DNA tumor viruses such as human papillomavirus (HPV). The objective of the current systematic review study was to present conducted studies in the field of HPV infection and its possible role in retinoblastoma.MethodsFor this systematic review, all relevant original research studies were assessed by searching in electronic databases include PubMed, Embase, Scopus, Google Scholar, and Web of Science by using relevant keywords. The study was designed based on the PRISMA criteria. All publications with English literature and original researches are considered for screening.ResultsConducted search results lead to 4070 studies. The title and abstract screening lead to 11 studies. Data extraction was performed on 8 included studies. The prevalence of the HPV was ranged from 0 to 69%, and HPV genotype 16 and 18 were the most detected types. The most used method for the detection of the viruses was PCR, and the most assessed sample was formalin‐fixed, paraffin‐embedded tissue blocks.ConclusionThe association between HPV and retinoblastoma is still inconsistent. The prevalence of the HPV in RB was ranged from 0 to 69%, which indicates a wide range and highlights the importance of further investigation for more accurate statistical of HPV prevalence in RB. Thus, further worldwide studies of larger sample sizes of cohorts should be investigated to clarify this uncertainty.     

Vulval cancer and HPV vaccination in recurrent disease

A woman diagnosed with a recurrent vulval carcinoma after initial treatment with radiochemotherapy is presented. After three additional relapses she was vaccinated with Gardasil. She has had no relapses in her vulvar area for 39 months and an overall progression‐free survival of almost 24 months.     

Assessment of Health Literacy in College-Age Females to Reduce Barriers to Human Papilloma Virus Vaccination

Assessing an individual’s healthy literacy and cultural background is important when discussing any health issue. This review explores specific concepts on HPV health literacy and how health disparities can influence college-age students’ knowledge about HPV-associated cancer and the importance of obtaining the 3 sequential doses of the Gardasil HPV vaccine. This information is relevant to practicing nurses, nurse practitioners, and midwives who provide direct individual care to adolescent and college-age students. Practical questions are asked to promote health literacy, provide culturally sensitive care, and reinforce health education on HPV, cervical cancer, and the HPV vaccine.     

蚌埠地区3408例女性宫颈HPV感染状况及基因亚型分布

目的研究蚌埠地区女性宫颈人乳头瘤病毒(HPV)感染状况及基因亚型分布特征,为该地区疫苗接种、宫颈癌早期防治提供数据参考。方法选取2016年7月至2019年12月在蚌埠市第一人民医院及周边社区医院进行HPV检测的门诊、住院患者及健康体检女性3 408例,采用聚合酶链反应(PCR)-膜杂交法进行HPV 21种基因分型检测,并对结果进行统计分析。结果 3 408例受检者中共检测出HPV感染阳性患者810例,总检出率为23.77%,各年龄段比较差异有统计学意义(χ²=1.712,P<0.05),单一感染模式人数最多,占全部阳性患者的73.09%,主要亚型为HPV16型;多重感染模式中,以二重感染人数居首,占全部阳性患者的19.39%,占全部参检人数的4.61%,主要亚型组合为HPV16型+HPV52型;亚型分布中高危型占85.31%,低危型占14.69%,高危型位列前五名的分别是HPV16(4.67%)、HPV52(3.55%)、HPV58(2.88%)、HPV51 (2.73%)、HPV53 (2.61%);低危型位列前三名的分别是 HPV6(1.41%)、HPV...     

HPV and Cervical Cancer: Updates on an Established Relationship

Abstract

Despite cervical cancer being considered a preventable disease, it still remains the second most common malignancy in women worldwide, with a higher incidence in underdeveloped countries. Human papillomavirus (HPV) is considered the causative agent of cervical cancer. The major mechanisms through which HPV contributes to neoplastic initiation and progression include the activity of 2 viral oncoproteins, E6 and E7, which interfere with critical cell cycle tumor suppressive proteins, p53 and retinoblastoma (Rb) protein. However, HPV infection alone is not sufficient to induce malignant transformation, and other significant cofactors contribute to the multi-step process of tumor formation, such as individual genetic variations as well as environmental factors. However, these cofactors are not important in the absence of HPV. Papanicolaou testing (Pap smear) and HPV DNA testing are tools used in the screening and diagnosis of cervical neoplastic lesions. Vaccination against HPV appears to be cost-effective in the prevention of HPV infection. A thorough understanding of the mechanisms that underline HPV carcinogenesis may result in the development of sophisticated targeted therapeutic approaches, such as antisense oligonucleotides against HPV oncoproteins.     

深圳市罗湖区女性HPV筛查阳性感染与宫颈病变关系

目的探讨女性人乳头瘤病毒(HPV)感染与宫颈病变的关系,为宫颈病变的防治提供依据。方法对本院2016年11月1日至2018年10月31日筛查HPV阳性病例资料进行回顾性分析,同时行TCT(液基细胞学)检查,以病理检查结果作为诊断标准。结果 2622例HPV阳性患者纳入本研究,病理检查结果阳性有204例。有2030例单一HPV感染,592例多重感染,单一感染中病理阳性的病例均为高危型HPV感染;HPV感染最多的是31-40岁组,为38.98%(1022/2622),最少的是>60岁组,是2.02%(53/2622),但是,>60岁患者中宫颈阳性病变最多,达22.6%;TCT检查616例为阳性,其中宫颈病理阳性有131例(131/616,21.3%);高危HPV诊断准确度为8.3%(144/1742),TCT准确度为21.3%(131/616),两者比较差异有统计学意义(P<0.01)。结论深圳罗湖区女性HPV高危型感染宫颈病变率高,不同年龄组宫颈病变阳性最多的HPV亚型不同,TCT对于宫颈病变的诊断准确度高于HPV筛查。     

女大学生HPV疫苗的接种意愿及影响因素分析——基于健康信念模式

目的了解浙江省女大学生自费接种人乳头状瘤病毒疫苗的意愿,以健康信念模式为框架分析女大学生自费接种人乳头状瘤病毒疫苗的影响因素,为今后开展健康教育活动及制订干预措施提供参考依据。方法采用自行设计的关于女大学生人乳头状瘤病毒的认知及人乳头状瘤病毒疫苗自费接种意愿调查问卷对302名女大学生进行调查,并采用单因素及多重线性回归分析。结果302名女大学生接种人乳头状瘤病毒疫苗行为意图得分(3.39±0.79)分,人乳头状瘤病毒疫苗的评价、知觉易感性、知觉到障碍、自我效能及行动线索是影响人乳头状瘤病毒疫苗接种行为意图的因素。结论浙江省女大学生自费接种人乳头状瘤病毒疫苗的意愿一般,受多种因素影响。     

透景HPV检测试剂在高危HPV DNA检测及宫颈上皮内瘤变筛查中的应用

目的评价国产透景试剂(透景HPV)用于HR-HPV DNA检测及宫颈病变诊断的有效性和可行性。方法 602例来自医院门诊健康体检的妇女或者宫颈上皮内瘤变(CIN)住院治疗的患者,经病理学明确诊断。采用透景试剂和Roche试剂(cobas HPV)平行检测子宫颈脱落细胞标本,比较两种方法的一致性。以病理诊断结果作为金标准,评估透景试剂和Roche试剂筛查子宫颈上皮内瘤变的敏感性和特异性。结果透景试剂与Roche试剂总一致率为94.62%(Kappa=0.881),阳性一致率为96.85%,阴性一致率为90.53%;透景试剂与Roche试剂HPV16、HPV18及其他12种高危型HPV的总一致率分别为95.92%(Kappa=0.906),98.70%(Kappa=0.885)和92.76%(Kappa=0.805)。校正后两种检测的总一致率为98.51%(Kappa=0.967),阳性一致率为98.87%,阴性一致率为97.81%;校正后HPV16,HPV18及其他12种高危型HPV的总一致率分别为97.40%(Kappa=0.940),100%(Kappa=1.00)和97.58%(Kappa=0.950)。透景试剂筛查CIN2+的敏感性和特异性分别为91.52%和52.06%,Roche试剂筛查CIN2+的敏感性和特异性分别为91.52%和54.29%,无统计学差异(P0.05)。结论国产透景试剂与进口Roche试剂检测HR-HPV的一致性高,是有效的HPV DNA检测方法,可用于人群中宫颈癌和癌前病变的筛查。